The biopsychologist Zala Slabe is the first person to have successfully proven the link between the presence of the neuropeptide PACAP in the brain and mood disturbances, especially depression and bipolar disorder.
At the age of 24 the holder of a master’s degree in biopsychology went to Amsterdam to study under the world famous neuroscientist Prof. Dr Dick Swaab at the Netherlands Institute for Neuroscience, which is part of the Dutch Royal Academy of Science and Art. At the Institute, where she continues to work, she has access to one of the rare brain banks in the world, and is the only in the team of scientists analysing brain samples.
As the young scientist explains, biopsychology is little known in Slovenia, while abroad it has been a recognised field of study and a science for years. Biopsychology is the knowledge of biological genetic predispositions which are later reflected in our behaviour, emotions and so forth.
The scientific discipline provides an answer as to why we behave in a particular way, where difficulties with mental health originate, and why there are differences between different people.
"By getting to know the biopsychological background of an individual and balancing biological functions, our contribution to public mental health would be much better," says Zala Slabe with conviction. She has always been interested in the biological and neurological parts of psychology, and in the explanation of our behaviour, emotions and psyche.
Analysis of human brain samples
At the Institute in Amsterdam, where with access to a brain bank which stores 4,000 deep-frozen human brains Slabe has outstanding conditions for research, the biopsychologist received the assignment of being the first to establish the presence of the neuropeptide PACAP in human brains. She used post-mortem samples from patients with bipolar disorder and depression. She also sought differences in the hypothalamus related to gender, and determined what the differences are between groups of control patients and those who suffer mental illness.
In her research she arrived at important findings, specifically that the neuropeptide PACAP is significantly expressed in women and those who have mood disorders, such as depression and bipolar disorder.
"The greater expression in women can offer us an answer to the question why there is a prevalence of mood disorders in women," she explains.
As is the case with serotonin and dopamine, chemical substances in the brain that are varyingly present in people and which can be balanced through medication (therapy), PACAP is also typically varied in expression, but we know nothing yet of balancing it. It is precisely PACAP that could signify the missing part in the puzzle of understanding our mental health, believes Zala Slabe.
Effect of PACAP on mental health
The research being conducted by Slabe has a clear objective, which is to help people and develop appropriate therapeutic strategies. Mood disorders are a major public health issue in today’s society, and her discovery could have an important effect on their treatment. Understanding the PACAP system in the human hypothalamus is key to the further development of therapeutic methods of treating mood disorders such as depression and bipolar disorder, and it is associated with post-traumatic stress disorder and other psychiatric disorders linked to stress.
"The higher expression of PACAP we have found in women points to them being more prone to neuropsychiatric diseases. This is caused by interaction with the hormone oestradiol, so we anticipate the development of treatment being linked to the balancing of oestradiol," explains the scientist.
Research in the field of Alzheimer’s disease
As her research continues, it will also include the brains of those who suffered Alzheimer’s dementia. She divides these into two groups, those with Alzheimer’s disease and depression, and those that did not suffer depression alongside Alzheimer’s. "Fifty percent of patients with Alzheimer’s suffer depression, which seriously increases the burden on patients and carers and is often a reason for hospitalisation. In Slovenia, 35,000 people have Alzheimer’s, and it occurs in 5.05% of the population of Europe, which represents an additional socio-economic burden. Previous pharmacological therapies with antidepressants improved the symptoms of depression in only around 50% of patients," says Slabe.
The neuropeptide PACAP has never yet been researched in connection with Alzheimer’s disease in post-mortem human brain tissue.
The biopsychologist is convinced that further study could make a major contribution to understanding this disease.
It is known that PACAP dysregulation can cause depression. The development of specific treatments that could balance the neuropeptide PACAP could also then contribute to delaying the onset of Alzheimer’s disease.
What further research promises
Current pharmacological antidepressant therapies improve symptoms through complex mechanisms that are not fully understood. Research into the neuropeptide PACAP system provides a broad picture, since it enables a better understanding of the actual functioning of the neuropeptide, gender differences in the human brain and the spread of neuropeptide disorders. "A knowledge of its functioning signifies an important contribution to the development of (gender-specific) psychopharmacological treatment," notes Slabe, who highlights that PACAP research also plays a vital part in controlling the onset of neurodegenerative diseases, the percentage of which in the modern world is increasing owing to the ageing of the population. With the development of treatment to regulate the PACAP system, we can ensure a lower incidence of depression, which indirectly contributes to the progress of Alzheimer’s disease. "The population is ageing and along with this the drive to research this disease and discover medication and treatment is growing, so researchers are seeking various targets, and PACAP could be one of those," she adds.In the future, Zala Slabe wants this kind of research to start being conducted in Slovenia, too.
"I want to transfer the experience I am gathering abroad to Slovenia, both in terms of techniques and the founding and development of some organisation or institute that would support the storage of post-mortem brain tissue. Establishing such an organisation would enable all the neuroscientists in Slovenia to research neuropsychiatric disorders. Having the possibility of such research would be extremely useful."
Date: 26. June 2019
Time to read: 6 min